In this report I’ll go through details of mthodology and criteria used for determining DDR deficiency in cancer samples from HMF and PCAWG. I have also included preliminary results towards the end.
DDR pathways and genes that are studied come from the following paper: https://doi.org/10.1038/s43018-020-0050-6
Pleasance et al. determined deficiency of 12 DDR pathway examining somatic sequence of 181 genes involved in those pathways, whether as core or accessory genes. Some genes were involved in more than one pathway. Out of 181 genes, 4 genes whose entries were absent in grch37.ensembl were dropped (“BABAM2”, “FAAP100”, “FAAP20”, “FAAP24”). These genes were only involved as accessory components. Therefore, in this study we will use 177 genes in total. A table of genes and their pathway(s) can be found below:
N.B. Genes that are accessory in some pathways and core in others have more than one row.
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## 2x_mut_pathogenic deep_deletion loh_only
## 109 392 170182
## loh,mut_likely_pathogenic loh,mut_pathogenic loh,mut_vus
## 553 1904 1481
## mut_likely_pathogenic mut_pathogenic none
## 523 972 4705
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## 2x_mut_pathogenic deep_deletion loh,mut_likely_pathogenic
## 109 392 553
## loh,mut_pathogenic loh,mut_vus mut_likely_pathogenic
## 1904 1481 92
## mut_pathogenic none
## 180 275
N.B. SSA pathway is co-deficient in 54 four cases but in none of them it has the absolute maximum. That’s because all 4 core genes in SSA are also core genes in other pathways and it’s unlikely for SSA to be selected.
Overall the number of samples are lower comparing to Pleasance et al. work. This could partly be explained by the fact that our cohort (n=7049) insludes both primary (n=2310) and metastatic (n=4739) cancers while their cohort only consists of metastatic tumors (n=570).